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Head and neck squamous cell carcinogenesis: Molecular and genetic alterations

Authors
Charles M Rudin, MD, PhD
Shanthi Marur, MD, MBBS
Section Editor
Bruce E Brockstein, MD
Deputy Editor
Michael E Ross, MD

INTRODUCTION

Squamous cell carcinogenesis in the mucosa of the head and neck involves the progressive accumulation of a large series of genetic abnormalities in genes regulating cell cycle progression, mitogenic and differentiative signaling pathways, angiogenesis, and cell death. This mutagenic progression, called multistep carcinogenesis, parallels the genetic model of colorectal carcinogenesis [1,2]. (See "Molecular genetics of colorectal cancer".)

Evidence for a mutational progression in tumorigenesis of head and neck squamous cell carcinoma (HNSCC) first derived from cytogenetic studies that demonstrated nonrandom clonal losses, duplications, and rearrangements of chromosome segments in head and neck tumors [3-5]. Within many of these regions of recurring chromosomal abnormality, candidate oncogenes or tumor suppressors have since been identified, some of which appear to play critical roles in carcinogenic transformation. Subsequent detailed progression models for carcinogenesis of the head and neck have been based upon mutational models and differential gene expression [6,7]. More recently, we have a better understanding of the mutational landscape in HNSCC from newer sequencing technologies [8-10].

Identification of some of the critical genetic events leading to head and neck cancer has clarified the molecular basis for epidemiologic observations regarding risk factors (eg, tobacco), identified previously unknown risk factors (eg, human papillomavirus infection), and is yielding information that may be critical for risk stratification. (See "Epidemiology and risk factors for head and neck cancer" and "Human papillomavirus associated head and neck cancer".)

In addition, these studies have unveiled a new series of targets for chemotherapeutic and chemopreventive intervention, which ultimately may result in more rational and successful therapies for this disease. (See "Chemoprevention and screening in oral dysplasia and squamous cell head and neck cancer".)

FIELD CANCERIZATION

The term field cancerization was first used to describe observations from microscopic examination of 738 lip, oral cavity, and pharyngeal carcinomas [11]. The grossly normal epithelium adjacent to the cancer in this study frequently contained dysplasia, carcinoma in situ, or invasive carcinoma, as though the entire mucosal field had been damaged and preconditioned by a carcinogen.

                     

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Literature review current through: Nov 2016. | This topic last updated: Tue Nov 24 00:00:00 GMT+00:00 2015.
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